The Surgeon General has stated that environmental and lifestyle changes may hold the most promise for the treatment of obesity. Gaps in knowledge about the physiological and behavioral control mechanisms on which dietary and environmental factors operate impede progress toward effective therapies. Thus, the goal of this Program Project is to integrate multi-disciplinary perspectives to investigate, using both human and rodent models, the environmental basis of obesity. It seems clear that under conditions where highly palatable, energy-rich, food is available continuously, energy balance depends on the ability to inhibit eating when food or stimuli associated with food are present. Examining how information provided by the cue properties of food can inhibit ingestive behavior is the central aim of this program project, with individual projects examining three levels of inhibitory control. First, inhibition of food intake may depend on the ability of orosensory stimuli, such as taste and flavor, to signal the nutritive consequences of eating. We will investigate the idea that animals use these sensory properties to anticipate the nutritive impact of foods, and that impairing this anticipatory response disturbs energy regulation. Second, we will study how signals that are detected by post-oral, gastrointestinal sensors are transmitted to the brain to suppress eating, and how the functions of these gut cues is influenced by dietary factors. Finally, the information provided by orosensory and gastrointestinal signals must be integrated and processed by the brain to produce adaptive behavioral outcomes. We will investigate the possibilities that inhibition of eating and appetitive behavior relies on the hippocampus, a brain structure that appears to play an important role in behavioral inhibition, and that certain dietary factors may promote energy dysregulation by impairing hippocampal function. Expertise in psychological, behavioral, biological, and food sciences will be integrated with the aim of discovering specific behavioral or dietary interventions that could strengthen or reinstate adaptive inhibitory control over eating and thus, ameliorate, stop, or reverse current trends toward obesity. An Administrative Core will provide statistical consulting, data management and other organizational support and will monitor and evaluate all program activities. The Analytical Core will oversee, coordinate, and standardize technological and behavior assays that are used by all Program Project personnel.